The Clinical Epilepsy Section continues to study the clinical pharmacology of old and new antiepileptic drugs. Special emphasis has been placed on studies of two new antiepileptic compounds, progabide and flupirtine. Progabide has been studied pharmacokinetically in normal volunteers, whereas flupirtine is being evaluated both clinically and pharmacologically in patients with either complex partial or absence seizures. Flupirtine is especially promising in models of epilepsy, and preliminary clinical results are encouraging. A new protocol for the use of progabide, as well as gamma vinyl GABA, in children with the Lennox-Gastaut syndrome has been approved by the NINCDS-ICRS and will soon be initiated. Both these drugs are thought to act by increasing CNS levels of gamma amino butyric acid (GABA) a putative inhibitory neurotransmitter. Measurements of changes in CSF GABA levels due to the drugs will be correlated with their effects on seizure control. Drug interactions continue to be a major pharmacologic interest of the Section. Most recently, the interaction between phenytoin and carbamazepine has been evaluated using mass spectrometry methology. Carbamazepine was found to decrease phenytoin clearance, leading to significantly higher levels of phenytoin in patients taking both drugs together. Understanding of this effect could help avoid medication toxicity. The pharmacologic evaluation of antiepileptic drugs is coupled with efficacy studies, carried out by intensive monitoring techniques including videotape analysis of epileptic seizures with simultaneous telemetered EEG recording, and daily determination of antiepileptic drug levels. Future studies are planned to evaluate the specific patterns of hepatic microsomal enzyme metabolism of antiepileptic drugs by evaluating antipyrine metabolites.